Concomitant Use of Selective Serotonin Reuptake Inhibitors With Oral Anticoagulants and Risk of Major Bleeding.

Importance: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants associated with a small increased risk of major bleeding. However, the risk of bleeding associated with the concomitant use of SSRIs and oral anticoagulants (OACs) has not been well characterized. Objectives: To assess whether concomitant use of SSRIs with OACs is associated with an increased risk of major bleeding compared with OAC use alone, describe how the risk varies with duration of use, and identify key clinical characteristics modifying this risk. Design, Setting, and Participants: A population-based, nested case-control study was conducted among patients with atrial fibrillation initiating OACs between January 2, 1998, and March 29, 2021. Patients were from approximately 2000 general practices in the UK contributing to the Clinical Practice Research Datalink. With the use of risk-set sampling, for each case of major bleeding during follow-up, up to 30 controls were selected from risk sets defined by the case and matched on age, sex, cohort entry date, and follow-up duration. Exposures: Concomitant use of SSRIs and OACs (direct OACs and vitamin K antagonists [VKAs]) compared with OAC use alone. Main Outcomes and Measures: The main outcome was incidence rate ratios (IRRs) of hospitalization for bleeding or death due to bleeding. Results: There were 42 190 patients with major bleeding (mean [SD] age, 74.2 [9.3] years; 59.8% men) matched to 1 156 641 controls (mean [SD] age, 74.2 [9.3] years; 59.8% men). Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OACs alone (IRR, 1.33; 95% CI, 1.24-1.42). The risk peaked during the initial months of treatment (first 30 days of use: IRR, 1.74; 95% CI, 1.37-2.22) and persisted for up to 6 months. The risk did not vary with age, sex, history of bleeding, chronic kidney disease, and potency of SSRIs. An association was present both with concomitant use of SSRIs and direct OACs compared with direct OAC use alone (IRR, 1.25; 95% CI, 1.12-1.40) and concomitant use of SSRIs and VKAs compared with VKA use alone (IRR, 1.36; 95% CI, 1.25-1.47). Conclusions and Relevance: This study suggests that among patients with atrial fibrillation, concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OAC use alone, requiring close monitoring and management of risk factors for bleeding, particularly in the first few months of use.

Gabapentinoids and Risk for Severe Exacerbation in Chronic Obstructive Pulmonary Disease : A Population-Based Cohort Study.

BACKGROUND: North American and European health agencies recently warned of severe breathing problems associated with gabapentinoids, including in patients with chronic obstructive pulmonary disease (COPD), although supporting evidence is limited. OBJECTIVE: To assess whether gabapentinoid use is associated with severe exacerbation in patients with COPD. DESIGN: Time-conditional propensity score-matched, new-user cohort study. SETTING: Health insurance databases from the Régie de l'assurance maladie du Québec in Canada. PATIENTS: Within a base cohort of patients with COPD between 1994 and 2015, patients initiating gabapentinoid therapy with an indication (epilepsy, neuropathic pain, or other chronic pain) were matched 1:1 with nonusers on COPD duration, indication for gabapentinoids, age, sex, calendar year, and time-conditional propensity score. MEASUREMENTS: The primary outcome was severe COPD exacerbation requiring hospitalization. Hazard ratios (HRs) associated with gabapentinoid use were estimated in subcohorts according to gabapentinoid indication and in the overall cohort. RESULTS: The cohort included 356 gabapentinoid users with epilepsy, 9411 with neuropathic pain, and 3737 with other chronic pain, matched 1:1 to nonusers. Compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation across the indications of epilepsy (HR, 1.58 [95% CI, 1.08 to 2.30]), neuropathic pain (HR, 1.35 [CI, 1.24 to 1.48]), and other chronic pain (HR, 1.49 [CI, 1.27 to 1.73]) and overall (HR, 1.39 [CI, 1.29 to 1.50]). LIMITATION: Residual confounding, including from lack of smoking information. CONCLUSION: In patients with COPD, gabapentinoid use was associated with increased risk for severe exacerbation. This study supports the warnings from regulatory agencies and highlights the importance of considering this potential risk when prescribing gabapentin and pregabalin to patients with COPD. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research and Canadian Lung Association.

Effect of Music Tempo on Pattern Reversal Visual Evoked Potential in Young Adults-Multisensory Stochastic Resonance: A Pilot Study.

Stochastic resonance (SR) is a phenomenon in which an intermediate level of noise enhances the response of a weak input signal. This phenomenon is experimentally used for rehabilitation and treatment of visuomotor disorders associated with low amplitude and higher latency P100 VEPs. We presupposed that shortly it will be possible to develop and design new devices that enable multisensory SR in the audio-visual modality for human sensorimotor enhancement and rehabilitation purposes. This study was newer in which the auditory noise was used in the form of song of different tempos and their amplitude and latency of P100 PRVEP (pattern reversal visual evoked potential) was compared. Whether the different tempos song may affects the PRVEP. This study was conducted on 57 healthy volunteers in AIIMS Bhopal. The subjects were placed in front of a computer displaying a checkerboard 8x8 size. Electrodes were pasted on their scalp. The average latencies and amplitudes of the PRVEP were recorded at resting, then with the stimulus of acoustic noise in the form of low and high tempo song. The PRVEP were recorded for each event. We found that low- and high-tempo songs do not affect the latency component of PRVEP, while it significantly affects amplitude. Music therapy can help with vision rehabilitation, especially in patients with low amplitude PRVEP. A more significant number of samples for further study in this field in multisensory SR with visual evoked potentials (VEP) are necessary. We can also conclude that a sound-free environment is essential during VEP recording.

Oral Anticoagulants and the Risk of Dementia in Patients With Nonvalvular Atrial Fibrillation: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of dementia. Oral anticoagulants (OACs) are essential for stroke prevention in NVAF, and studies have shown a possible protective effect on dementia. However, findings have been inconsistent and hampered by methodological limitations. Thus, we assessed whether the use of OACs is associated with a decreased incidence of dementia in patients with NVAF. In addition, we explored the impact of the cumulative duration of OAC use on the incidence of dementia. METHODS: Using the UK Clinical Practice Research Datalink, we formed a cohort of all patients aged 50 years or older with an incident diagnosis of NVAF between 1988 and 2017 and no prior OAC use, with a follow-up until 2019. Patients were considered unexposed until 6 months after their first OAC prescription for latency considerations and exposed thereafter until the end of follow-up. We used time-dependent Cox regression models to estimate hazard ratios (HRs), adjusted for 54 covariates, with 95% CIs for dementia associated with OAC use, compared with nonuse. We also assessed whether the risk varied with the cumulative duration of OAC use, compared with nonuse, by comparing prespecified exposure categories defined in a time-varying manner and by modeling the HR using a restricted cubic spline. RESULTS: The cohort included 142,227 patients with NVAF, with 8,023 cases of dementia over 662,667 person-years of follow-up (incidence rate 12.1, 95% CI 11.9-12.4 per 1,000 person-years). OAC use was associated with a decreased risk of dementia (HR 0.88, 95% CI 0.84-0.92) compared with nonuse. A restricted cubic spline also indicated a decreased risk of dementia, reaching a low at approximately 1.5 years of cumulative OAC use and stabilizing thereafter. Moreover, OAC use decreased the risk in patients aged 75 years and older (HR 0.84, 95% CI 0.80-0.89), but not in younger patients (HR 0.99, 95% CI 0.90-1.10). DISCUSSION: In patients with incident NVAF, OACs were associated with a decreased risk of dementia, particularly in elderly individuals. This warrants consideration when weighing the risks and benefits of anticoagulation in this population. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with NVAF, OAC use (vs nonuse) is associated with a decreased risk of dementia.

Concomitant Use of Selective Serotonin Reuptake Inhibitors and Oral Anticoagulants and Risk of Major Bleeding: A Systematic Review and Meta-analysis.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs), the most prescribed antidepressants, are associated with a modestly increased risk of major bleeding. However, in patients treated with both SSRIs and oral anticoagulants (OACs), the risk of major bleeding may be substantial. OBJECTIVE: To assess the risk of major bleeding associated with concomitant use of SSRIs and OACs, compared with OAC use alone. METHODS: We searched MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials (from inception to December 1, 2021) for clinical trials and observational studies assessing the association between concomitant use of SSRIs and OACs and the risk of major bleeding. Given sufficient homogeneity of studies, we conducted a random-effects meta-analysis to estimate a pooled hazard ratio (HR) of major bleeding associated with concomitant use of SSRIs and OACs, compared with OAC use alone. RESULTS: The review comprised 14 studies, including 7 cohort and 7 nested case-control studies. Following assessment of clinical and methodological heterogeneity, eight studies with a total of 98,070 patients were eligible for the meta-analysis. The pooled HR of major bleeding associated with concomitant use of SSRIs and OACs was 1.35 (95% confidence interval [CI]: 1.14-1.58). In secondary analyses, the pooled HR for concomitant use of SSRIs and direct OACs was 1.47 (95% CI: 1.03-2.10). CONCLUSION: Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding. Overall, our findings suggest that physicians may need to tailor treatment according to individual patient risk factors for bleeding when prescribing SSRIs to patients using OACs.

Femtosecond Laser-Assisted Intraocular Lens Fragmentation: Low Energy Transection.

PURPOSE: To describe a case of femtosecond laser-assisted hydrophobic intraocular lens transection. METHODS: Case report. RESULTS: Femtosecond laser-assisted transection of a one-piece acrylic hydrophobic intraocular lens for explantation via a small surgical incision was successfully performed with low energy parameters. CONCLUSIONS: This case illustrates a novel and effective clinical application of the femtosecond laser. [J Refract Surg. 2017;33(9):646-648.].

Recurrence and chronic pain after mesh fixation with skin staples versus sutures in Lichtenstein's inguinal hernioplasty: a retrospective cohort study.

PURPOSE: Reduction in operating time has been reported with skin staples instead of original technique of mesh fixation with sutures in Lichtenstein's hernioplasty. Few studies have been conducted, however, with inadequate follow-up and variable results. We have undertaken this study to compare the duration of surgery and incidence of recurrence (beyond 1 year) and chronic pain after mesh fixation with staples versus sutures. METHODS: In this retrospective cohort study, adult males with primary unilateral inguinal hernia who underwent open Lichtenstein's hernioplasty from January 2009 till October 2010 were included. All patients with recurrent hernia, concomitant surgery, follow-up less than 1 year and missing data were excluded. Data collection was done via questionnaire and telephonic interviews. Outcomes are recurrence, chronic pain and duration of surgery. RESULTS: We reviewed 70 patients in each group. At median follow-up of 21 months (range 12-34), there was 0 % recurrence in both the groups and chronic pain was 4.4 % higher in suture versus staple group (11.4 vs. 7 %, p value = 0.7). Median duration of surgery was 30 min higher in suture as compared to staple group (90 vs. 60 min, p value = 0.004). CONCLUSION: Our study confirms that staples are superior to the sutures due to shorter operative time and do not cause any additive risk of recurrence or chronic pain. Prospective trial with long-term follow-up for each patient is required to validate these findings in order to generate definite guidelines.

Risk factors of gallbladder cancer in Karachi-a case-control study.

BACKGROUND: Gallbladder carcinoma (GC) is a relatively rare malignancy worldwide but is the second commonest gastrointestinal cancer in Pakistani women. Gallstones have a positive association with GC but other factors also influence in causation. METHODS: This is a retrospective case control study over a period of 19 years. The cases (Group A) were patients with histopathological proven carcinoma gallbladder (N = 60) and controls were patients with cholelithiasis but no carcinoma gallbladder on histopathology (N = 120). Multivariate regression analysis was done to calculate the odds ratio, 95% confidence interval and P-Value. A positive relationship was found between size of stone > 1 cm, solitary stone, age > 55 years and multi-parity in women. RESULTS: There were 60 patients in Group A and 120 patients in Group B. mean age of diagnosis in Group A patients was 57 ± 2.4 years while mean age of diagnosis in Group B patients was 48 ± 1.35 years. Sixty seven percent of cancer group patients were female as compared to 78% females in non-cancer group. In Group A, 69% of female patients were multiparous (parity of more than 5) while 43% of group B patients were multiparous. For body mass index (BMI), both groups were not very different in our study population i.e. around 78% patients in each group has BMI of more than 23 Kg/m2. In Group A, 37% (n = 22) have solitary stones as compared to 15% (n = 18) in group B. similarly Group A patients has larger stone size as compared to Group B i.e.59% (n = 36) patients in Group A have stones of more than 1 cm when compared to 35% (n = 41) patients in Group B. After using multivariate regression analysis, age more than 55 years (OR - 7.27, p value- < 0.001), solitary stone (OR - 3.33, p value - 0.002) and stone of more than 1 cm (OR - 2.73, p value - 0.004) were found to be independent risk factors for development of gallbladder cancer. CONCLUSION: Most of the patients (78%) with GC were female, and the statistically significant risk factors were older age, solitary stones and stones size more than one centimeter. A case can be made for prophylactic cholecystectomy in such a high risk group. However a population based study is required to calculate the true incidence of GC in Karachi and a prospective multi center study is needed to produce strong evidence for screening and prophylactic cholecystectomy. TRIAL REGISTRATION: As this was a retrospective review of medical records, as per institution policy, its gives waiver from any registration (ethical/trial).

Hepatic vein and inferior vena caval thrombus extending into the right atrium: a rare complication of amoebic liver abscess.

Amoebic liver abscess is an endemic in developing countries but few cases of associated vascular complications have been reported. The authors report a very rare vascular complication of hepatic veins and inferior vena caval (IVC) thrombosis extending into the right atrium in a young male with large amoebic liver abscess. Optimal result was achieved with early diagnosis on CT scan, percutaneous drainage of abscess, intravenous metronidazole, peri-operative anticoagulation, sternotomy and thrombectomy.

Intussusceptions in adults: clinical features and operative procedures.

OBJECTIVE: To determine the clinical presentation and treatment outcomes of adult patients with intussusceptions. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from January 1988 to December 2008. METHODOLOGY: Medical records of patients with diagnosis of intussusceptions in adults (above 15 years of age) from January 1988 to December 2008 were retrieved through ICD 9 coding system. Patients with complete records were included in the study and those with incomplete medical record or under 30 days follow-up were excluded. Data was analyzed on SPSS version 16. The treatment outcomes were hospital stay, 30 days-morbidity, mortality and recurrence of intussusceptions during follow-up period. RESULTS: The mean age of the 19 patients was 37 years with male predominance. Most patients presented with acute bowel obstruction. In 14 patients, small bowel were involved. CT scan diagnosed intussusception in 10 out of 12 patients. Benign lead point were found in 80% cases. Eighteen patients were treated surgically. Fourteen (70%) patients underwent resection with primary anastomosis while in 4 patients only reduction was done. In resection group, 11 patients had resection after reduction and in 3 patients only resection was done. There was no recurrence in resection group. One recurrence was noticed in the reduction group and one patient died of advanced gastrointestinal malignancy in the nonoperative group. CONCLUSION: Intussusception is a rare cause of acute intestinal obstruction in adult population. CT scan is a promising diagnostic tool to establish pre-operative diagnosis. Early surgical resection could achieve optimal outcome. Small bowel intussusception could be reduced before resection if there is no doubt about bowel viability. In most of the patients the lead point could be benign disease.

Amoebic liver abscess: experience in a south Asian country.

Amoebic liver abscess (ALA) is endemic in south Asian countries. The current study was undertaken in order to evaluate the clinical spectrum, management and outcome of ALA at an urban tertiary care hospital in Pakistan. The chart notes of 232 ALA patients admitted from 1 January 2000 to 31 August 2007 were retrospectively reviewed. The most frequent clinical findings included: fever (96.5%); right upper abdomen pain (80.2%); liver tenderness (73.5%); tachycardia (61.6%); hepatomegaly (60%); nausea and vomiting (42%); and jaundice (23.9%). The duration of symptoms was less than 14 days in 70% . Ultrasound examinations revealed 69% of the abscesses were in the right lobe, 19% in the left lobe and 12% in both lobes. The size of the abscess was greater than 5.0 cm in 83%. Seventy-seven percent of the patients had a single abscess and 23% had multiple abscesses. Ultrasound-guided therapeutic aspiration was performed in 64%, but 36% were treated with antibiotics alone. Metronodazole was the most frequently used antibiotic. However, various combinations of antibiotics were also used without any obvious justification.

Ileosigmoid knotting- a rare variant of bowel volvulus.

Two patients with acute intestinal obstruction underwent exploratory laparotomy after adequate fluid resuscitation and radiological imaging. A preoperative diagnosis of sigmoid volvulus and an operative diagnosis of ileosigmoid knotting or compound volvulus were established.

Acute mesenteric venous thrombosis: improved outcome with early diagnosis and prompt anticoagulation therapy.

AIM: To analyze the clinical spectrum of acute mesenteric venous thrombosis (AMVT), to assess the factors affecting the outcome and to determine the optimal management of this disease. METHODS: We retrospectively reviewed the case records of 20 patients with acute mesenteric venous thrombosis confirmed on CT imaging or on laparotomy over a 23 year period. Patients were divided into two groups according to the duration of symptoms: group I with symptoms for up to 3 days duration and group II with symptoms for more than 3 days. RESULTS: The mean age was 50.55 year, with 15 male and five female patients. In all patients the diagnosis were confirmed on CT imaging preoperatively except two patients when the diagnosis was established on exploratory laparotomy in the period before 1998. There were six patients in group I and 14 in group II. Five patients underwent an operation and one received a non-operative treatment in group I. Three patients underwent laparotomy and 11 received non-operative treatment in group II (P-value 0.01, Fisher's exact test). There were three and one mortality in groups I (n=6) and II (n=14) respectively (P-value 0.061, Fisher's exact test). Most patients received preoperative therapeutic anticoagulation. Two patients in group II who underwent exploratory laparotomy, neither did receive preoperative anticoagulation. Both patients died in the postoperative period. Eighteen patients were investigated for thrombophilia. Eleven patients had one (n=6) or more (n=5) identifiable hypercoagulable state, these included protein S deficiency (n=1), both protein C and S deficiency (n=5), polycythemia (n=2), factor V Leiden deficiency (n=1) and malignancy (n=2). None had antithrombin III deficiency, hyperhomocystine urea and contraceptive pill intake. There were no statistical differences between thrombophilic and non-thrombophilic patients regarding duration of symptoms, indications for laparotomy and 30 days mortality rate. CONCLUSIONS: Patients with AMVT of rapid onset (<3 days duration) had poor outcome and more patients required laparotomy because of extensive thrombosis leading to bowel gangrene and peritonitis. Early diagnosis with CT scanning, prompt treatment with anticoagulation in all patients, surgical treatment in cases of peritonitis or failure of medical treatment can contain the mortality rate in these patients.

A unique variant of intestinal tuberculosis.

Duodenum is a rare site of involvement in intestinal tuberculosis. We report a 19 years old boy who presented with nonbilious vomiting and weight loss. His workup showed stricture in ascending colon, multiple liver abscesses with pneumobilia on CT scan. Upper GI endoscopy revealed stricture in 2nd part of duodenum distally. He was operated and duodenojejunostomy with limited right hemicolectomy (for stricture in this part of gut) were done. Biopsy report was suggestive of tuberculosis. Antituberculous treatment was started. He responded well and gained 20 kg weight at 3 months follow-up.

The clinical significance of antinucleolar antibodies.

BACKGROUND: The importance of antinucleolar antibodies seen by indirect immunofluorescence on HEp-2 cells, although associated with systemic sclerosis (SSc), in unselected patients is unknown. AIMS: To determine the true clinical significance of antinucleolar antibodies in an unselected patient population. METHODS: Antinucleolar antibody (ANoA) positive samples were identified in the immunology laboratory during routine autoimmune screening tests; case notes were reviewed using a standard proforma. RESULTS: 104 patients with ANoA were identified and ANoA+ samples were subclassified into homogeneous, clumpy and speckled antinucleolar types. SSc was evident in only two (1.8%) patients. Other connective tissue diseases were identified in 33 patients (32%); 22 patients (21%) had evidence of various malignancies. Both disordered liver function and anaemia were seen in 22 patients and were the commonest laboratory abnormalities. CONCLUSIONS: Neither the presence nor subtype of ANoA is specific for systemic sclerosis. Laboratory comments appended to results should reflect this fact.

Screen-detected breast lesions with an indeterminate (B3) core needle biopsy should be excised.

BACKGROUND: Screen-detected breast lesions in the National Health Service Breast Screening Programme (NHSBSP) are assessed by core needle biopsy (CB) or fine needle aspiration cytology (FNAC). Most core biopsies are diagnostic and representative, but a small proportion is indeterminate (coded "B3" in the NHSBSP). We studied the surgical outcome of screen-detected breast lesions with indeterminate (B3) CB. METHODS: We retrieved and analysed the data on women who were recalled for assessment of a screen-detected abnormality in whom the initial CB was reported as B3 over a six-year period from a prospectively collected database in one breast screening centre. The main outcome measure was final histology following surgical excision. RESULTS: Among 4080 CB performed, 220 (5.4%) were B3. Mammographically 127 lesions were microcalcifications and 88 were soft tissue lesions. On surgical excision (n=199, 90%), 67 (34%) were malignant. In patients with malignancy, clinical examination, US and concurrent FNAC were either suspicious or definitive of malignancy only in 2%, 4% and 7%, respectively. CONCLUSION: A third of screen-detected breast lesions with indeterminate CB are malignant on excision. Clinical examination, US, and FNAC may identify some of these carcinomas pre-operatively but most malignancies would not be picked up. Thus, these lesions should undergo surgical excision.